Table 3.
Mechanisms of ciprofloxacin resistance in different bacteria.
| Bacteria | Mechanism of resistance | References |
|---|---|---|
| Neisseria gonorrhea | 1. Target-site modification (gyrA SNPs: S91F, D95N, and D95G, in the QRDR and parC SNPs: D86N, S88P, and E91K, in the QRDR) 2. An overexpressed NorM efflux pump |
(85, 86, 89) |
| Neisseria meningitidis | 1. Mutations in the QRDR of the gyrase-encoding gene gyrA [Ile (I) or Phe (F) mutations at position 91] ✓ Further mutations in gyrA (D95N and T193A) and parC (D86N, S87R, and E91G) have been linked to increased ciprofloxacin MIC 2. The Over expression of the MtrCDE efflux mechanism (by two distinct mutations in the mtrR gene) |
(92, 93, 95, 97–99) |
| Pseudomonas aeruginosa | 1. Target-site modification (Most common: replacement of Thr at position 83 in GyrA is by Ile and the Ser at position 87 in ParC by a Leu) 2. Efflux overexpression (MexCD-OprJ, MexEF-OprN, MexAB-OprM, and MexXY-OprM) |
(13, 100, 105, 107) |
| Campylobacter jejune | 1. Single point mutation C257T in the gyrA gene 2. Overexpression of efflux pump CmeABC 3. Inverted repeat (IR) in the cmeR–cmeABC intergenic region |
(113, 114, 118) |
| Haemophilus influenza | 1. Amino acid changes in the QRDR of the topoisomerase II and I genes ✓ gyrA (Ser84 and Asp88) and parC (Gly82, Ser84, and Glu88) had more amino acid changes than gyrB and pare |
(119) |
| Escherichia coli | 1. Mutations in the DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) are a major contributor to resistance [gyrA mutations (Nucleotide substitutions at codon 83)] and additional mutation, most commonly at codon Asp87 2. Overexpression of AcrAB-TolC, (the principal efflux pump)and AcrEF and EmrAB 3. Decreased expression of OmpF |
(123, 124) |
| Salmonella | 1. Increased efflux (a primary mechanism) 2. Decreased production of the OmpF porin 3. Mutations in gyrA and parC |
(125, 126) |
| Legionella | 1. Mutation in the gyrA/gyrB and parC/paeE (mostly mutations affecting codons 83 and 87 of the gyrA QRDR) | (127) |
| Moraxella catarrhalis | Amino acid substitutions in gyrA and gyrB gene (Amino acid substitution of Thr80 to Ile in GyrA: low-level resistance) | (130) |
| Acinetobacter | 1. Expression of the efflux pumps. (AdeABC pump) 2. Presence of quinolone resistance (qnr) genes located on the plasmid, (low-level resistance) 3. Mutation in quinolone resistance-determining regions (QRDR), where the target enzymes of DNA gyrase (gyrA) and Topoisomerase IV (parC) |
(133) (138) (135) |
| Enterococci | 1. Chromosomal mutations in gyrA and parC ✓ Resistance-associated mutations have been discovered in the gyrA gene (Ser83Arg, Ile, or Asn; Glu87Lys, Gly) and the parC gene in E. faecalis (Ser80Arg, or Ile; Glu84Ala) ✓ In E. faecium, mutations in the gyrA gene (Ser83Ala, Leu, Ile, Tyr, or Arg; Glu87Leu, Gly, or Lys) and the parC gene (Ser83Ala, Leu, Ile, Tyr, or Arg) have been identified 2. Overexpression of active efflux (NorA in E. faecium and EmeA in E. faecalis) 3. Target protection (Qnr-like determinants), Binds gyrase, described in E. faecalis |
(139, 140, 142) |
| Staphylococcus aureus | 1. Mutations in the QRDR of DNA gyrase and topoisomerase IV ✓ ParC is major target. The secondary target is DNA gyrase, which is less sensitive 2. Overexpression of the efflux pump NorA |
(145, 147) |
| Mycobacterium tuberculosis | 1. Mutations in the genes encoding gyrase, most commonly in the QRDR of gyrA, but sometimes in the QRDR of gyrB ✓ The most prevalent mutations in gyrA are found in the QRDR codons 88–94, particularly codons 88, 90, 91, and 94 ✓ FQ resistance in gyrB is often linked to mutations in codons 500 and 538 2. Overexpression of The Mmr efflux pump and other efflux pumps include antiporters LfrA and Tap, in addition to the mycobacterial pentapeptide MfpA and the ATPase complex Rv2686c-Rv2687c-Rv2688c operon |
(152, 154, 159) |
CIP, ciprofloxacin; QRDR, quinolone resistance determining region; MIC, minimum inhibitory concentration.